« Making Sense with Sam Harris

#98 — Into the Dark Land

2017-09-20 | 🔗

In this episode of the Making Sense podcast, Sam Harris speaks with Siddhartha Mukherjee about his Pulitzer Prize winning book, The Emperor of All Maladies: A Biography of Cancer

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This is an unofficial transcript meant for reference. Accuracy is not guaranteed.
Today's podcast here, I think, is a really important conversation. It is a conversation about cancer and before You decide that you don't feel like listening to a conversation about cancer. Please reflect on the fact that you or someone close to you will almost certainly get it. This is just a virtual guarantee My father died of cancer. I've had friends die of cancer. On. One of my own family has cancer. Now this is just All around you, whoever your and today's is one of the great authorities on the topic you ve heard him before the podcast, but today I was begin with the Mukherjee about the topic with which he is most closely associated said. Dorothy Is a cancer physician and researcher he's an assistant professor,
medicine at Columbia, university and staff, cancer physician at Columbia and why you Presbyterian Hospital, he's a former road scholar. He graduated from Stanford and Oxford where he received a phd step in cancer causing viruses. From Harvard Medical School and his laboratory, focuses on discovering new cancer drugs using various biological method he's published everywhere. You expect, but he's also a regular writer for the new Yorker and he has won the Pulitzer Prize for his book. The emperor of all maladies, biography of cancer, Conversation ranges widely from his experience, non colleges. Ask him many questions from both a patient and doktor centred point of view. How to think about a cancer diagnosis, the biology of cancer, how
The mapping of the human genome has changed our understanding cancer and the possibilities of treatment how cancer spreads. We talk about whether were always getting cancer and simply fighting it. We talk about the difference between remission and cure. But how much of cancer is due to environmental causes. There's a lot here greater to another hour of said Arthur Time, so without further delay. I bring you said Arthur Mukherjee. I am here was a dark Mukherjee said Arthur thanks for coming back on a pike ass, my letter. Thank you. So the last time round. We spoke about your more recent book, the gene which was fascinating and also let us a little further afield. Then at least you realize we would go. I had just come fresh off my controversial podcast with Charles Marie.
And then Numb lead us into a discussion about the genetics, have intelligence or suspicions of such and exhausted both of our interest. If not our patients on that topic, I won't do that again this time round, because we're talking today about your book for which you are certainly best known and for you won the Pulitzer rise the emperor of all maladies, biography of cancer, you are a and oncologist and spend a considerable- your time working with patience and also to research into the biology of cancer, so I am really looking forward to having this conversation, because we only at about ten minutes last time round to touch on this all too important topic first list. For we get into the biology of cancer and treatment. What's your
story here in terms of how you got into becoming an on people tend not to think about, how that the different medical specialities dictate a very different experience from the the site the doktor- and I can imagine that being an ear doc is not at all the same as being a dermatologists. You don't get caught, I was in the middle of the night when you're dermatologists your beer, not constantly seeing people die out engineer you're dealing as much with human rights, de as with actual health concerns. First, what what is the experience of being and on and because it seems like it would be emotionally very challenging, and how did you decide to take this on yourself? So I came into cancer medicine a little bit in reverse aid in the nineties I was at Oxford. I was training as an immunology is my granted workers and aiming immunology. I was interested in vaccines him that this is a time,
and the immunity revolution was taking off and it was researchers and the biological media just figured out and find the most important things. What how the immune system works, how it might allow for enabling acceleration in support. So I went to accident, I studied viruses and when I was in immunology sinner by Rollo, just by training the one particular wires tat. I got interested in is actually a major human pathogen Epstein bar virus Evie,
and had the reason that we still deal with a visit. It's rather strange viruses that lives in the human body, but doesn't seem to cause overt disease I'll come back to the world of work in a second, but virtually all of us have seen barber as this is a virus that's evolved with us with human and the human species, for tens of thousands, hundreds of thousands of years and in other maybe seventy to eighty percent of people are infected in some parts with dvd, and it seems, Our immune system, doesnt seem to reject it and we never clear it during our lifetime. So the question I was interested in is: why is it that we dont care Epstein barbarous, whereas in if you have an influenza, you had the flu you got the flu, your body clears the flu and you don't have flu virus left in your body. Was the difference between these two things? Why is it the flu get?
cleared by while DVD remains persistent and I tried to solve it, I published mean I helped partly so that mystery, but then it became obvious to me. You read the the epidemiology of E b b. It turns out that in fact, the sword it doesnt Gaza worked disease, but in fact there is a long history of it being links to various cancers, including them farmers and other cancers. In fact, it is a bit the links between avian and cancer, quite deep, and so I began if it became more interested in cancer becoming more and more of a consequence. The genetics. Why is it that what genes and be allowed to do the things that it does? Why is it able to stay? Persistent in the human host amend type became incident? Cancer
and, as I became more and more in cancer, became more and more interested in going to meet up thinking about cancer medically and then became an on college. So I sort of did my I came. The cancer through the world of science and immunology and it so it's only interesting immunology, as you might know, what's suddenly come alive in the world of cancer again the question you always either: what is it, what it is like to being? What is it like being in oncologist weights. It's it's very, unlike the examples it s very unlike being in the emergency room, because you, you need two things change.
Dreamily quickly get the things that I knew were absolute certainties in ten years about five years ago. So I think one of the things about being an oncologists is that you, the amount of information in the under the rapidity with which it with which, if changes is striking things that I knew as absolute certainty is ten years or up in question now, I'm gonna ten years ago, if someone told me that we would be manipulating the human immune system to reject cancers, I would say our chances of that being true, I pretty minor. Ten years later, you know that's the new direction of cancer. Oh that's what is surprising things you don't get up in the middle of the night like a surgeon. Might or as often as a certain might. But you stay up,
in the middle of the night, because your finding out new things that wouldn't be the case ten years ago. Do you with children as well are only adults. I do all I work with adults, although within the word of cancer. Leukemia is one area that are particularly interested in its a funny. It's a funny story. Sandy leukemia further. For the longest time, blood cancers led the charge in the science and treatment of cancer, and what we can we can expect why they sort of deep reasons. Why and then, and now the world of cancer is moving beyond leukemia is looking for your hobby. How to take those lessons? and learn them in in solid cancers like breast cancer and lung cancer, so so I see both. I see all I see, but mainly I'm still interested in luck, cancers
the history here again now, folksy, not so much on the disease, but on the the doctor patient experience there really: was this amazing stigma associated with cancer? I recall, a story about my own grandmother who I never met, who died before I was born where she had metastatic melanoma and was in the hospital. Really to die, but I believe, is true to say: but she was never told her prognosis at all. In fact, she was lied to about what it was. I think she was told she had arthritis and would recover on. Theirs is something so unthinkable: at this moment it used about how widespread this practice was. But I've heard from from many other sources that that it was routine for Doc, to lie to patients about their prospects, especially women, patience and sometimes in collaboration with there, husband and those. If there's one point your book, were you painted a picture of it?
very flattering picture of of one of them. People you studied under, I believe, was Thomas Lynch, lung cancer, specialist and you decide armed him. As a kind of virtuoso of telling people bad news, but there was a kind of Correct me if I'm wrong, but there seem to be a kind of necessity of shaping the truth. Even there. How do you think about this? What was the practice there? and and and what is the practice now in terms of delivering bad, who's. In a context of real uncertainty, because it seems to me that oncologist must in many cases take rest huge in uncertainty, because even in the most dire circumstances, there are still the store is of the end of the Irish. They indeed less than five percent cases, where some one makes it cover, even from some fairly dire stage for diagnosis. It's a complicated issue, as you point out as an important question.
And I think they d the capacity to take refuge in uncertainty. That is an important philosophical question. Actually I mean you know: to what extent are human beings allowed to take refuge under uncertainty and add to what extent does not become a kind of opium opium? So I think I think I'll colleges are very individual styles around this, but there is the one thing I think you learn in
in cancer is, is a pope is, is negotiated, negotiable and that you never get your way through up an individual's individuals journey with your patients journey through their cancer. I think the most important thing that, with that I try to convey the patience and I picked a field has tried somewhat now, is to convey that uncertainty without without sort of washing it up and cleansing it. Instead, living it? And that's a tough question, that's a tough thing didn't convey because on one hand there is the d, a hard statistics, But, on the other hand, there there are the individual suits. Where do you lie within the day, the distribution of patients who are likely to die in vain,
months or whether you will be the one your patient happened. What will happen to be the one who will survive at that time? I think that the most honest way of dealing with it is is, it is, is a kind of work is to imagine. This is a process that, on day one when you when I meet someone, I can give them the bare statistics and then that I try to also describe what the outliers look like who isn't outlier, why? I think they were outliers? Is it because of the location of the cancer? They had the genetics of the cancer, the genes that the cancer limitations? Is it because they happen to have a particularly successful surgical reception? Is it that they were the best response to that particular chemotherapy such described that, and I tell people honesty that I dont know where they would set, but my but this, but but but the but the curve,
we mean the median look like this and then in time the neck I meet them. I know a little bit more and so on modified my understanding if you wanted to have a formal name for it. This is Beijing statistics. It's it's a wise. We are thinking about the world when you take your priors and modify your prayers to make conclusions about how these people, how individual will behave. Given the circumstances I think a written about it. I think bays insight into the world Thomas bases in some of the worst very profound yeah and medicine, is still trying to deal with. It were coming to terms with that idea again in terms of your emotional experience. As a physician, I remember one point book I had, I think you are describing what it was like to be a residents that point in the house since changed, but you were talking about a kind of profession, Liz of your
national range in the presence of these distraught families or visa or patients who, for whom you have to deliver, varies Harry News- and you were talking about that as a kind of necessity, but also as a perhaps a a psychological or ethical error. I know you want you weren't, you obviously more comfortable with this change. It was coming over you. How you had this was becoming you had a routine way of distancing yourself from the pain in order can you gotta dampening down your your your empathy. So as not to be bold, Over every time you had to talk to her a very sick patient. How is that evolved for you and is there? Is there optimal way of being in that role, I dont know doesn't
to my way of being a droll everything that you have the conflict that you're talking about his very important because the deed, the professionalism of empathy is is, it is a rather die or thing, as you can imagine it creates. It creates all sorts of internal conflict, something you know that there are now classes off with which, which hope to professionalized medical empathy that the good things about that there is a kind of it. There is a kind of importance to two sets: tivoli training. If you wanna call up anything, it's an unwelcome word, testimony training in medicine
But that said, I think I think, there's also a regret that people have the spontaneity that you had, but when you were a resident when I was a reason, when there was an intern, be able to tell people sort of honest news about themselves is somehow being filtered. He feels it there's a filter that come into your life. I think I personally try to resist the future. I try to maintaining honesty. I told you my method. My method is to think in. If you want to call it formally a kind of Beijing way about medicine I think that that helps I ate. It allows you to maintain a kind of personal honesty in the face of so so. When someone says to me am I gonna die in five months. You dont resort to the kind of you. No nonsense. Speak of the eight units of professionalized empathy.
In in which you in a hand and pretend to be aggrieved. You try to assess yourself what your own feelings about their impending gap. As you try to understand, you try to help its it, as I think, the real struggle and, and- and I and I know like like many disciplines- ivy be it the exaggeration can be can ultimately, the exaggeration of false empathy is detected by patients were quickly and they shut themselves off the last thing we want to hear his words empathy, so so so I think it's you you'll be appointed, Barton struggle that's very much in inside the discipline, and there are probably dont want a physician who burst into tears. And begin sobbing on their shoulder, when he delivers a news, so there's not, you can't beat you can't be,
ride when your own eyes out loud with tears. So I've written about this, I wrote an essay for that. Worker on on numbness it, which is about this idea, and about trying to connect life as a doctor and how it becomes you. What would look the fastest response to two living as a doctor is to do to shoot down to two to become none to it to all the enormity of the suffering, and I was that there is something in what one the connections I saw it in there in that, peace was, was to check off, who was a doctor and a writer and about his his capacity remain clear, eyed about about about the world without shutting off without becoming none to it. It's a pretty tough act, bread, I think,
I think the dry yeah what's it is amazing to witness as also watch the documentary based on your book, that can burns produced and given this is so far outside the range of my professional experience. I just was amazed at what oncologists have to go through as their patients go through, The scariest moments in their lives and especially when you're talking to the parents of children who have received a diagnosis of leukemia or some other cancer is just so lasserate in. For me. Viewer, as goes, is very good of me to watch until I just kind of surrendered to it. But basically, for me it's just the continuous effort to stifle too
years seen people go through that labour and images to it. Just to remind you and your readers, your lesson is that, of course, the point you are making is incredibly important, which is they eat your daddy? You cannot no one wants to sobbing doctor and you want someone. You know there is a fundamental and I asked. I suspect that, though I will raise some hackers- and I say this as a fundamentally the fundamental relationship between a patient and the doktor. Even today, the power lies in one direction. The doktor knows that the patients are there to try to seek help. That is not to say that that's a good thing. It is just to remind ourselves that there is a that that be empty can be helpful and, of course,
requisite for medicine, befalls empathy and and trying to trying to trying to try to emulate. The actual experience of the patient as a doctor is gonna, be necessarily flawed. You, you are not the person with cancer. It is that it is in the person of sitting in front of you that has the real that has the problem, so I fear that there's a good distinction on enough. You know the psychologist Paul Bloom at Yale. The he's done a lot of work. Empathy and is he wrote a very controversial? Book entitled against empathy where he differentiated what he calls cognitive empathy, just understanding what another person's expired, it is, and the more emotional contagion style of empathy where you just fine, yourself crying. When you see someone is sad gathering in this case he would say What what we want are physicians, who I have a lot of
cognitive empathy. They know what you are very likely to be going through and they care to alleviate your suffering, but they're not being held hostage by their own emotional reaction to suffering by carry We threw you are thinking about. We know how I feel with it. If it were my kids, I was talking about and all that absolutely and end- and you know it comes down to again day very impulse
basic things. Is that I mean in the in the laboratory when we study cancer, genetics, austerity, cancer cell behaviour, your abstracting away so much from the experience of the illness. But it's important to remember the experience of the of the illness lived through the lives of your patients as well as what tomorrow, better motivates elaborately life, at least for me, so I think it's very important. Adding an indistinct I've seen you read this distinction between between the admission of empathy d, the consultation of empathy and the enactment of it, and am I
I would agree that I think that's it. That's an important distinction and I think it's a struggle. It's not simple. I dont think you I'll be lying. If I say to you that one doesn't led into the other quite quickly- and this I think goes back to the idea across the board that in a behavioral sense you can teach being a doctor, but that but of course that's just million a behavioral sense. What does it mean to behave? One word to say about the big patients, a very quick you pick up the idea of your saying them without believing them the believing it believing inside what it means to have. If you want to call a cognitive empathy is, is it is a psychological round which is actually quite deepen under studied, actually mean really understand. It is early anything that you know
the side of bean and on colleges that you think cancer patients or their their family members should know, but but often don't in terms of the experience of of receiving a diagnosis and and going through treatment and talk into their doctors, and this is only a question you would ask your doctor or anything you, do differently, given how much you know about wisely. To be a non colleges and without the full course of treatment, often is and just what, what? What does your experience give you as a prospective cancer patient, that most people don't have. But one of the things I am thinking of, of an important essay, which I often encourage patients to read by steam gold. While the media is not the message in which the back story is that Stephen
Gimme a good. It was diagnosed with a very unusual cancer abdominal mesothelioma, and if you read the statistics of votes was prognosis was extremely grim. There was very, very sobering and be the question that gold asked himself in this. I say, and I encourage people to read. It is if you take. If you take the curve of survivors, ship So you know if you just blocked as it, you can block number of patients who lie five months. Seven months, twelve months, twenty months after diagnosis,. It looked like a might, look like a gas incur, but might have any kind, but neither like any kind of curve. The question what
ask yourself is: where are you located in that? Are you wonder? You know you on the side of the kind of person who is gonna, be rapidly succumb to this cancer? I likely to survive the battering of surgery radiation and give it their be. If you do, what are the chances that you were survivors with? Meaningful life had separate cetera, so he tried to place himself and once he had placed himself in that curve, he was able to make decisions about treatment more and more accurately. So so if I were to become a patient- and I will admit statistically speaking, you and I were both likely- have cancer at Vienna, one in two men, one and three men. I won three women, pardon me and again, statistically speaking, we feel that this is a good chance that we will die of cancer.
If I were a patient I'll, try to ask that when I was out of sitting on the other side of the desk, as it were outright to locate myself, Stevens Gold, it and say: what's the likelihood that I will be one of the few people who will succeed with some kind of novel there be
this is the chances that I won't and once I know that I might be able to make decisions in b the thoughtfully that the questions that I like to ask myself is: what are the one of the strong and points that I should stop treatment. I'd ask my doctor that what are you looking for when you would say to me? You know, I think we're were getting to point of time that we'd better consider seriously consider a hospice seriously consider the job. What are those, what are those endpoints advice and, in the opposite sense, what are the one of the things that you that without you're looking for- and I will tell you- this- is a kind of pit patient and I would rather treat more aggressively treat more proactively then, with whip
Thirdly, this is not to say that a specific and and palliative care are not proactive treatments. Please don't make no less on make that mistake, but but this is just to remind us that that that's the that's the direction that at that, those are the those are the kinds of guidance that I'd like to know. I may add it could be hard science, it could be genetics it could be. You know the micro environment. It could be that the nature of the tumor I'm looking for. I'm looking for I'm looking for a hitchhikers guide to Beijing, cancer wrote the fact many people are dying of cancer and and will continue to die from cancer is in some perverse way, good news, because it shows that many of the diseases that killed us before we even had a chance to get cancer have been cured, or at least beaten back into submission. Let's talk about the disease itself and I am sure that the other questions
come up here relevant to the patient experience because, as you say, virtually everyone will either get cancer or have someone close to them, get it so. The simplest possible question for which no doubt there is some, no perfectly simple answer, but what is cancer? Cancer is a family of diseases that shares the common characteristic that sells don't stop dividing. I dont know how when, and they don't have a normal regulation that would they would stop dividing, sometimes says, don't know when to die, a combination of which leads to unfettered cellular growth. Often the cellular brought spreads outside the primary site and then continues to grow and
second, replaces breast cancer growing in the bone or in the brain and ultimately leading to death because of the uncontrolled unfettered growth of cells. So a cure for cancer would be a treatment that stuff This unregulated cell growth, without harming normal cells or the normal process of cell division, was that if there were such a thing as a generic cure, would it be described that way, that's correct. It would be described as a mechanism way that we would be able to kill the cancer cells grilled without preventing normal cellular growth and remember normal said it is not only responsible for growth in the common play sense. We understand it, but also wound healing and the fact that your blood cells continue to have an immune response. All of that is related to grow. So, in fact, stop
growth even in adulthood. The fact that your skin can heal itself. It is a consequence of cellular growth, so growth and attitude it continues and killing cancer cells growth while maintaining onset and what remains a big challenge now, of course, as we understand cancer more deeply and again, I've just written about this. This is why, in my mind, this is one of the things that my laboratory studies, which is that cancer cells grow, partly because they can, because the mutations genetic mutations allow it allowed the cells to have unfettered or unregulated growth, but it turns out that those that unfettered, unregulated growth is also control not only by the sell itself, but by the environment around it their signals, in the environment around ourselves that tell cells went to stop growing
Some of them are emanate from the cells themselves from within themselves from within their genes. Some of them emanate from things like when cells contact each other or the context in which they find cells, so that, when, when a normal wound heels into the cells in the healing wound: keep ground and growing until they reach each other and the something somehow a signal, a centre that everyone that you have and become a new tumor, doesn't become a new organ, doesnt become a new hand, so cats in cancer that process, not only of this of the cells owned signals to stop growth are disrupted, but also look. The cancer cells no longer receive the signals from the environment from the context that would normally prevent or or maintains that the normal Ziobro. So are we talking about multiple diseases here that are only superficial
similar or is there really a hope that there could be some generic foundational cure that you find they met. Yes, m that actually addresses malignant cell growth in principle, regardless of tumor type, regardless of the sight of a metastasis let loose field oscillate between between between these two points, the that that the reality is that there are there. There are absolutely some commonalities across cancers. And in fact has been a kind of there's been a kind of popular literature. Saying, oh, you know every cancer, its own disease. Therefore, you know there's no possible, that's that The idea is a reaction.
Over lumping of kitty, always splitting of cancers in reaction to the overlapping of cancer. From a prior decade, there are deep commonalities: Biff between different cancers. There are so called hallmarks that virtually all cancers share a man. It's important to understand that, Is that we still call this family of diseases under single umbrella has some scientific basis. These diseases, regardless of breast cancer, lung cancer, etc. Brain cancer girl astronomers share some deep commonalities and it's important to recognize it. You know it's not as if we just throw the whole thing in a pox and all of the all of the lumber is and that every cancer that something On the other hand, of course, we now know from deep sequencing and and and a deeper understanding of cancers biology,
but every individual tumor has its own spectrum of mutations and they can differ quite radically from one breast cancer. Drug must cancer, so we ve got to be able to take both those things into it, and and and both those things are simultaneously There will be some commonalities. There are some come now. Is that stretch across multiple cancers, and there are some uniqueness down to the level of an individual specimen of cancer and how's the secrecy the human genome affected the picture here, as this radically change changed our understanding of cancer and opened the door to new treatment or are we still in the mode of just hoping that a clear genetic picture which will give us some power here? The bottom line? Is cancer is a genetic disease. So and by genetic disease I mean that the fundamental cause of cancer is genetic mutations, accumulate in cells. These genetic mutations allow these cells. To
said before start undergoing unfettered, unregulated growth and sometimes unregulated, so death and thereby creating an imbalance in the regulation of built there. Has been no field in medicine. That has been more impacted by the sequencing of gene onto cancer medicine, given what we know about cancer genetic disease, but we based I'm not I'm sending the human genome project created a normal template for for understanding of cancer and against that normal attempt led me began to understand the mutations. Donations in cancer cells? We have now sequenced. Tens of thousands up to hundreds of thousands of cancers vary in in great depth and begun to understand the spectra. Mutations that are present, indifferent,
answers that knowledge has allowed us to conclude several things: One is allow us to conclude that individual specimens of cancer share some commonalities. I discuss some of them while we also have unique, unique Rustics- and you can imagine- this is a kind of Van diagram to individual specimens of breast cancer- will have some common mutations and they will have some despairing mutations. They'll have some Common behaviors they'll have some disparity unit behaviors. So it's about us to understand that number two brought its allowed us to understand the evolution of cancer, how cancer cells evolved from me so from a single cell, that's mutated, acquiring more mutations, a kind of
new, Darwin and understanding of of how cancer cells evolve in a human body over space and time? The number three its allowed us in in in cases to identify genetic pathways, our genes, the products of which can be targeted by medicines. So a classic example of this was a drug company back which is really a targeted therapy for a certain kind of leukemia. There have been more examples of this reception targets: the young, the abnormal
an act of a gene in in mostly in breast cancer, I'm so so the genetic revolution going all the way up to the human genome project has defined not just the biology of cancer in the evolution of cancer, but has allowed us to identify targets by which cancer has can be, can be targeted and and and and killed. That said, it also reveals some fundamental shortcomings. In many cases, the cats I'll give you the best example of into cancer that I work with the acute my lodgings leukemia M: L, a blood cancer. We ve I sequence, I would save virtually every patient that I c e gets a gene sequence, some sort of genetic sequence, many of those jeans that are mutated in these in this form of cancer. I don't have a therapy, for I don't have a treatment for
So I have knowledge but no way to treat or treat those cancers, and that's been that that men that's been surprising, but also disappointing, that that gene sequencing didn't pop out immediately with a dozen the new cancer targets that were immediately and ability to targeting using new new medicines. Perhaps we should step back to just took a fundamental point of of biology here. You're talking about cancer as being entirely a matter of what the genes are doing but course, everyone understands that there are many different ways to get cancer or least least raise your risk of getting cancer, and these are things like Smoking or getting too much sunlight were, can expose the various toxins or What do we know about why normal cells become malignant? How did the genes. That
regulate cell growth become disrupted, and I get a further question is, Do we know how many oncogene, there are at this point, is over how much of the genome are we thinking about and what we are trying to forestall this process in every form was the first question. You know there's a business. It is a rich controversy in the field of cancer medicine about the extent to which cancer causing mutations arise because of errors in so copying hopping. Dna replication, verses, environmental carcinogens that cause mutations. So, just to summarize the controversy, because it's important
There are two sources through which a cancer causing mutation could arise. One is you know something from the environment. The cosmic rays carcinogen from today the smoke enters. Your lung tissue goes into the long, seldom causes it, because a dna damage estimated resulting through a cascade of event, items resulting in a mutation, the other source,
is that, when a long so divides during that cell division like ourselves, it has to make a full copy of its genome to transmit the gene onto its daughter cells, but that process that process of copying like every popping process in biology, is error prone and it can make a mistake and into if we know instead of copying AC tv, it should be, could copy eighty g g by mistake and thereby introduce invitation, but these are to fundamentally different ways by which mutations could occur in humans, and the major question is the extent to which human cancers arise as a consequence of a versus be now were sunk ass. The answer is obvious: in lung cancer caused by smoking, the preponderance of mutations arise as a consequence of smoking. So there's no doubt about that, but for many other cancers we don't
No, exactly the role of a versus baby errors and seller application versus some kind of carcinogen that we haven't identified yet again, other it's been a real challenge in the field and went away into into some important territory here and perhaps controversial territory. Here, it's been a real challenge in the field to identify major human chemical carcinogens there. So clearly, tobacco is a major human
look a carcinogen, but since the ninety nine days, the number of major human chemical carcinogens that we identify has not been great great. A number viruses. Yes, but those are not chemical, Carson, their biological carcinogens. You could say obesity, absolutely there's a lincoln in obesity and cancer, but you know calling obesity. A chemical carcinogen really stretches the definition so and we found lots of other things. The things that can cause cancer, but their impact on human populations remains still relatively modest in terms of epidemiological number. So that's why the fields there's a controversy brewing in the field in a back to back papers and important journals, challenging each other's data from extremely prominent laboratories, and on the word I'm saying you know we ve underestimated the amount of cancer
caused by cellular application. If so, then the problem is, you know, handle the seller replication problem other saying day it's easier than theirs. Great or hidden or unknown environmental carcinogen. Or maybe it's in its death by a thousand cuts. Maybe there are many, many of them each with small impact, and this is a major controversy in the field. Is there any sense of the percentage that is due to endogenous genetic mutations, verses contamination from the outside, whether weathers with toxin, or a virus, so so this this answer, I'm gonna have to give your squarely answer to this, because firstly depends entirely on cancer. So enough, it's lung cancer. In the context of tobacco smoke, the tobacco smoke is totally preponderant, wrote if its cervical cancer, that is lucky you know very, very strongly linked to a virus, but but their cases
which we don't know exactly. Why answer, for instance, the baby, the arena around breast and prostate cancer very controversial areas, and if I would If I would stick out a number you'd get fifteen phone calls tomorrow singer the number was wrong and they would be right because you just don't know just to clarify- and this is important- nothing? I mean I know you're the podcast emphasizes this just because we don't know doesn't mean its unknowable wrote it's very important. This is an incredibly consequential question, and perhaps this is that this goes back to the conversation. We have around genetics in an intelligent centre right. These are questions that we we have to have a clear eyed answer to designate. There should be some there's. There should be some scientific clarity, because its consequences, if it turns out that in
cancer d, the seller application, plays an important role that leads to important policy implicate. We cannot turn our eyes away from it. Does that an unsafe gushing? I wish it was not the case I wish there was, a carcinogen that I could eliminate from the environment that would dramatically decrease their rate of breast cancer in women? I wish that was the case absolutely. I wish that was the case, but we don't find it then we can turn our eyes away from it and say: that's not the reality. And the related part of my question about the ongoing in themselves do. We know how many genes we're talking about that regulate, cell division and and can be but there are hundreds, and they really did classically these two coming to flavors, the so called aka genes and tumor suppressor genes. Aka genes can be imagined accelerators in a car. So when you have an accelerator, if you jammed
celebrated by a mutation. The car conscript moving the tumor suppressor is are counteract this. They were considered like the breaks in the car and the a car, and when you snapped the brakes, then you can't stop the car so Uncle June the tumor suppressor, where the two classical examples of genes. Now there are more, there are genes that I thought to be jeans that create that create the d, a platform or in the cellular environment which encourages mutation, though there there surf of mutated, James, the end. They don't even more fascinating category landscaper genes. These are genes that allow cells to change or the interaction with their environment, but that their cancerous behaviour can become more easily man.
Best today out there a variety of classes of genes- and we are now talking about really hundreds of genes drawn across the human genome. These, I believe you wrote about this dynamic in your recent New Yorker piece of it that seem to describe aid slightly different logic of metastasis, I used to be thought that the problem is simply that the cancer cell is moving from the side of the primary tumor and going elsewhere. But now you describing the soil it lands and is just as relevant is the seed that his landing. What do we know? about the relationship between the sight of primary tool. Wars and where metastasis is likely to happen. If, in fact, it happens it, neither is there a privilege route from primary lung cancer to somewhere else or or a primary liver cancer to some
or else I mean yeah. I think he's a new year article that, but you know, if they're going to get bone cancer, it's a rare to see bone cancer of the hand and this programme on an accident who have. What do we know about the spread of cancer in the body is very unusual to see metastasis, for instance, in Bonn, metastases happen in Bonn, with some bonds are spared widely, while other ones are not spared, and it said that we still don't know why it has to do so. For for the longest time we used to think that you know, rare cells escaped the primary tumor and those resources, once they arrive at their destination sites. Vague sprout like seeds and take off, and that's what causes metastasis We now know that it's absolutely true that the process by which sells leave the tumor is important and is incredibly important. Work done by people like Robin Wine Bergen at MIT and other
Let us try to understand what makes what allows what enables it when you have a breast tumor, what enables some some sellers relieved that breast human and go into the circulation, but that's not enough and that's. The point is that I try to emphasise the extra something we work on in the lab We ve written papers about this, but what we now know is that, just because a say, in fact, when selves leave the primary tumor, they perish in vast numbers dame vast numbers of those cells once they enter the circulation with Bilbil, He killed either I mean system or by other, and they have to have specific protective mechanisms to escape that killing even when they arrive in their destination organs.
Even when they arrive in the destination organs. There are creditors in the definition of the moon cells that are watching out an income and and and and and removing these, these tumor cells. That's what probably makes metastasis I'd rather be rare event. That's why, even though hundreds of thousands of cells could be leaving a primate But only a few can a capable of causing metastasis and finally, we know that the capacity of a cell to sprout in in its in a foreign site when a breast cancer goes to the bone is not a coincidence. It is, only by creating a kind of malignant alliance with the sell the cells
already in that site than the normal cells and decide the bone cells. Can a breast cancer began to grow in the barn and to some extent, if you couldn't, if we could interrupt those alliances between the cells, we would interrupt the most deadly aspects of cancer, which is metastasis and not. What I'm saying is an important point which we just said: if only we could interrupt the processor cell division in. Cancer cells versus normal cells, we would achieve significant successes in cancer and yet an hour later, we also saying, if only we could interrupt the alliances between cells that form metastasize and their soil. We could achieve significant successes and cancer. We ve switched importantly, we ve begun to consider. We haven't switch focus. Of course the genes are important. It's of course it's important to stop cancer cells from dividing, but is equally important to think about this
I allowed the context in which those cancer cells learn to grow and some organs risk if more than their fair share of metastasize rises combatant, I live horizontal explained, it cannot be explained by the circulation. So it's not as if you know this debt there is the spleen and deliver are equally bathed in blood. The equally have strong supplies of blood, and yet the liver is a disproportionate side of metastasis. Why? The answer is in twenty seventeen. This observation was made in eighteen. Sixty two seventeen- we still basically dont, know why we want to make our liver is more like ours plans that we want to make one more like us means again. We need to find out what are the alliances that are being cultivated by ourselves abreast so interesting, lay cancers. Some individual types of cancer done metastasize to deliver their unlikely to be funded
we're. So it really is there. Some again goes back to point, there's some commonalities here and some differences that we need to understand. Is the picture. One of us always getting cans at some level and it never becoming truly pathological until it does mean that is that that the picture of an immune system that is based We always dealing with cancer from perhaps a very we point in life, or is that too simplistic an idea? That was not the picture ten years ago. That is one aspect of the picture today, which is to say that that we we now reconsidering the idea of the extent to which primary tumors an immune system is only one part of the story were reconsidering the idea whether primary tumors metastatic tourist, reconsidering the added to which, to what extent do these cells need to form alliances with normal cells with
What tissue in order to become cancers? To what extent does immune tradition stop cancers? The old paradigm used to come from doesn't just to give you just one example. If, if you take patients such as HIV, our patients who have AIDS they'd, they don't, they have a rather limited spectrum of cancers that arise as a consequence of their immune depletion. Other of the other immune collapse, so. We know what the other, certainly farmers, certain sarcoma, psychopathy sarcoma and certain other cancers, but other cancers don't seem to sprout up in these people who have proof only depressed immune systems and for a while that led us to believe that the immune surveillance a only operates on certain kinds of cancer viral cancers? You know cervical cancer is another example, and we thought that the virus
cancers. Unsurprisingly, were the ones that are most likely suppressed by immune system, because, of course, viruses. I recognized by the immune system but now, where revisiting that idea and asking whether we had missed some fundamental feature of the immune system, parts of it immune system that are less affected by I had some of these immunological diseases that may still play a vital role in suppressing tumors in in in human beings There's a concept of the war on cancer that when this was first initiated in the U S, it might have been Lyndon Johnson, but we ve had this experience have seen a succession of U S President's stand up. In n out something bold and hopeful about the the way in which the resources we put toward this disease will bear fruit in some reasonable timeframe, and I just been this- I think it's probably no present
has has declined this privilege, but in hindsight, is obviously very poignant to see the new confidence in and even bluster pinafore that this particular moon shot, and yet from the side of those who are dying from cancer and have died from cancer and their families. It seems like the moon is still quite far away how is the war on cancer going Asia and was the likelihood that the decade is going to look as bleak as some of the previous ones. In your view that you know it's a, it submits a mixed report at its height to give him the grades beds and mixed report. As you can imagine, I think we're doing an important kind of experiment in camps and today, which we want doing before an experiment has two or three phases. We now know, generally speaking,
when the number of women the tumor burden, the total number of cells is minimal. That statement it will itself generator flare of controversy. So I should I should modified somewhat. We now know that only detection of camp so I should I should modified somewhat. We now know that early detection of cancer is when we are correctly detecting cancers, when the only detecting cancer helps. Just to give you one country example: do you know you can detect thyroid cancer early, but an but a vast majority of these thyroid cancers are not likely to become pathological, so they dont cause disease. They looked like cancer under a microscope, but they dont cause disease, and this is this was a huge problem in South Korea, for instance, and I've written about it that in the past, so the correct
deployment of early detection helps. So that's point number one. The second thing is that, once its detected early, we now know that the deployment of of targeted Happy and possibly mean illogical therapy helps. So the second piece is that that we are learning to take the earliest the early detected cancers and apply therapies to them that are specific for that kind of cancer and to give some examples, her ceptin, as a drug for and an early date. Acted her to positive cancer, and then there are many other examples of this, which is not just breast cancer. There are other her to cancers.
It's still mainly breast cancer. That is that that is that that the her to her second is mostly a successful in there are other cancers that over express her to hear they tend to be very hard to treat with her. Second, it's really breast cancer, whether he said, but we're not talking about small numbers, so mean a brisk and significant advances in breast cancer with her ceptin and then, and then and then the third phase is to continue, may maintain and monitoring patients, even after their cancer has disappeared from their body, visibly disappeared from their body to catch or detect cancer as early as first the boy in their recurrence or in their or our or in the relapse or more only if new cancers arise so so this is a kind do I call this? I gave it a talk at that clinical oncology meeting recently. This is a kind of
a boy, a kind of new experiment we're in the middle of a bold experiment in cancer. I hope it works in the right direction. There are signs that way it would be worth but I think it would be. It would be an overstatement to say that we need to solve this peace. Mindful of your time said Arthur. At this point, I think I just have two more questions from a patient centred point of view, especially mindful of the fact that every moment you spend talking to me you're, not in your lab, curing cancer, so hope our listeners don't hold that against me, a fundamental question of knowledge here. What is the difference between remission and cure in your line of work and its very important difference, in fact that the world of cancer was it was on the first to recognise the differences between between these two words are remission is when you don't enemies, but very simply their technical definitions, Images when you don't have any visible sign of cancer in your body a cure
is when you don't have cancer? That's you don't have cancer period, you have been removed the possibility of relapsing or dying from that cancer breast cancer. A great example of this. We now know that you can relapse with breast cancer. Ten years, even twenty years after you ve been an intermission from your region, breast cancer, twenty years we need it is in many cases we know it's the same breast cancer because off Jean Sequencing, because you can seek- was the genes and cannot be a coincidence that the same mutations, it's on a new cancer, because the same mutations were found in the in the council that arose ten years afterwards. Which means that those cells must have been living in some kind of dormant state, invisible, dormant state, not causing metastatic relapse in those intervening tunnel
years, which in turn means why which in turn basically Why? Why, with ourselves and Howard ourselves, sitting Dormann and could be avoid that could be, we activate the new system somehow could be changed the soil somehow to make themselves less able to come back to life till so those are. The tools are the fundamental differences in in in some cancers like leukemia, chided leukemia. We know that there's been cured because those children have lived The full lives up to sixty seventy years. Without never would never having a recurrence of the original cancer, but even in those cases, do still talk in terms of remission. Amended is a treatment paradigm where the colleges will say we believe you have been you heard of your cancer, or is it always like the breast cancer, where a remission of the original cancer is still conceivable. It depends on the cancer. So again, surgical treatment is extraordinarily effective in cancer. Some cancer, solid cancers
If ever lung cancer, you remove the lung cancer, and the patient does not have early signs of a task as we follow these patients, but over time, you get more and more confident that the lung cancer is not likely to come back and their declared curate stored at some point of time are there some patients would relapse with lung cancer years later? Yes, but in breast cancer in particular its been up, it's been it's been particularly those in breast cancer We don't hesitate to use the word cure when you actually have strong evidence for the future and their patients were cured of cancer. As I said, surgical treatment for early localised cancer can be curative, but there's examples. I then it depends on the cancer that you know you remove. The fry me two minutes through surgery You gave the person chemotherapy to prevent any remnant pieces of orbit of cancer left over and ten. His later than relapse from breast cancer. So, finally said Arthur is a question that strikes me as as especially relevant to people going.
Rule treatment and when it, when they see what's on the menu and What what's on the menu is often a fairly toxic form of chemotherapy or, if its staff their protocols haven't work there, given some expense, mental trial, which also can be quite toxic even more toxic than then the standard approach may historically much of of what has been offered in the form of treatment has looked near. A pointless to people and the trade off between trying. To extend their lives under again under a condition of some impressive uncertainty. As to how much more life will be one and The quality of life concerned. Men do want to spend your remaining time toxify by the the treatment it becomes very difficult gamble and its again from the lay person side it see.
Very hard to think about, and especially so when, when you're too, when its apparent thinking about the experience of his or her child, do you have any wisdom to share out how one thinks about this- I guess you could you could I'd. Your answer in terms of cost standard protocols and the costs and benefits of going into something truly experimental work amino. We generally extremity protocols go to an evolution themselves. They begin their law lives as alternatives to standard protocols. Only when a patient has not had the expected response with a standard of. So that's what the best way begin. Then they implement interest. Second life when there have been compared sort of head to head against the standard for
and finally, they have another life when they become the be preferred or the first line of treatment. In contrast to the stand, a protocol and that's the desert, there's a systematic, systematic way in which their judged. So obviously, as as as someone who runs trials, your sensitive to this progression, you don't wanna put patients so an experimental protocols, men standing protocol that extremely lighted work and you dont want to mean that you know remember, remember: first, do no harm remains even in this new age of medicine. First do no harm is. It remains an important mantra, yet I often say
this is the only discipline where the web central oath is in the negative. A first job is to do no harm because it, but because the capacity for harm is so great, so so so I too, I think, generally advise people have to be mindful of this progression when the plan, the prospects for a standard therapy are extraordinarily bleak, based on statistical circumstances. Again I go back to this idea. Stephen gold and silver where'd. You lie where you said. Are you, like? it would benefit from from farming nonstandard therapy, and if you are likely to benefit, we should try it with the understanding that we have to be if it was. If we want briefly, if you didn't have equipoise about the capacity of that every succeed, we wouldn't be trying it, we would be, we would go going. Wait, wait without with blinders on so, rather than the other than doing that. I generally be mindful of this progressive. Remind patients and myself on this progression,
and finally, how do you think about in an experimental protocol, the ethics of pudding, half the patients on a placebo? trawl and- and what happens when you begin to get data that suggests that the treatment is actually effective to people. Rick protocols with some irregularities are giving the day her ceptin say when it was being stuck to every body and in the in the study or how does that work? It's an it's a thorny debate. We become a little bit more accepting off of cross over. Cause in which you can cross over from one to the other I'm later, but you know I've timidly that the purpose of random migration is to seal ourselves from our own biases. The purpose of animalization is to remind doctors that it's not because we are malignant peoples, because we're so awful and because patients are so we want badly these three
is to succeed and that we imagine, therefore wait. Wait where we are drawn to solutions and the purpose of random opposition is to remind us of the purity that that, if you really randomize you'd come out with the result that was successful now over time we learn to relax those rules somewhat, but they will not. Were fully be relaxed? In my relax, I mean we ve created mechanisms by which crimes can be stopped. Early even that, has some dangers so imagine, instead of using viable. As your end point you're, using some surrogate like you know, at some tumor market goes down or the breast cancer cells disappear. They become smaller, tumor shrinks. You could make a strong argument that ok, maybe too much talk a little bit, but it ultimately makes no difference. The patients are likely to die just as what we have been burnt by this in recent times, the use of surrogate. So as a field
I'm colleges are very, very mindful and remain mindful of that. Are there. That is their pressure because of hope job to be able to run transfers to absolutely. But but there is that there is a constant, thorny conflict about what the appropriate and points are and remain Open to discussion once again said: Arthur has been fantastic education talkin to you, and I just want to encourage you to keep firing on all cylinders, because you have a really beautiful career here, a fantastic rider. He right, big, comprehensive and extremely readable books. You write great article, are you spawn, documentaries and in and all of that you are a doctor and day bench scientists, so, I don't know what, where you get your extra hours in the day, but it's really wonderful to behold at leisure, a big fan of the backers of people to keep that work up. Thank you. So much if you find this podcast
able there are many ways you can support it reviewed on Itunes or stature. Whoever you happen to listen to it. You can share on social media with your friends, you can block. About her discuss it on your own podcast or even supported directly, and you can do by subscribing through my website at SAM Harris, DOT, org and there fine subscriber only content which includes my ask me anything episodes. He also get access to advance tickets to my live events as well streaming, video of something. Events, and you also get to hear the bonus questions from many of these interviews. All these things and more you'll find on my website at SAM Harris DOT. Org. Thank you for your support of the show.
Transcript generated on 2020-03-23.